The Nucleus is Irreversibly Shaped by Motion of Cell Boundaries in Cancer and Non-cancer Cells

Overview

Journal J Cell Physiol

Specialties Cell Biology
Physiology

Date 2017 May 26

PMID 28542912

Citations 26

Authors

Vincent J Tocco

Yuan Li

Keith G Christopher

James H Matthews

Varun Aggarwal

Lauren Paschall

Hendrik Luesch

Jonathan D Licht

Richard B Dickinson

Tanmay P Lele

Affiliations

Soon will be listed here.

Abstract

Actomyosin stress fibers impinge on the nucleus and can exert compressive forces on it. These compressive forces have been proposed to elongate nuclei in fibroblasts, and lead to abnormally shaped nuclei in cancer cells. In these models, the elongated or flattened nuclear shape is proposed to store elastic energy. However, we found that deformed shapes of nuclei are unchanged even after removal of the cell with micro-dissection, both for smooth, elongated nuclei in fibroblasts and abnormally shaped nuclei in breast cancer cells. The lack of shape relaxation implies that the nuclear shape in spread cells does not store any elastic energy, and the cellular stresses that deform the nucleus are dissipative, not static. During cell spreading, the deviation of the nucleus from a convex shape increased in MDA-MB-231 cancer cells, but decreased in MCF-10A cells. Tracking changes of nuclear and cellular shape on micropatterned substrata revealed that fibroblast nuclei deform only during deformations in cell shape and only in the direction of nearby moving cell boundaries. We propose that motion of cell boundaries exert a stress on the nucleus, which allows the nucleus to mimic cell shape. The lack of elastic energy in the nuclear shape suggests that nuclear shape changes in cells occur at constant surface area and volume.

Citing Articles

Correlation between female pronuclear/cytoplasmic ratio and number of chromosomes in mouse zygotic stage: implications for aneuploidy assessment in ART.

Xiao W, Akao S, Otsuki J J Assist Reprod Genet. 2024; 42(1):85-95.

PMID: 39585518 PMC: 11805731. DOI: 10.1007/s10815-024-03312-5.

Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization.

Wang T, Abolghasemzade S, McKee B, Singh I, Pendyala K, Mohajeri M Nat Commun. 2024; 15(1):10151.

PMID: 39578439 PMC: 11584751. DOI: 10.1038/s41467-024-54577-4.

A high-throughput microfabricated platform for rapid quantification of metastatic potential.

Bhattacharya S, Ettela A, Haydak J, Hobson C, Stern A, Yoo M Sci Adv. 2024; 10(33):eadk0015.

PMID: 39151003 PMC: 11328906. DOI: 10.1126/sciadv.adk0015.

Rethinking nuclear shaping: insights from the nuclear drop model.

Dickinson R, Abolghasemzade S, Lele T Soft Matter. 2024; 20(38):7558-7565.

PMID: 39105242 PMC: 11446230. DOI: 10.1039/d4sm00683f.

Nuclear shapes are geometrically determined by the excess surface area of the nuclear lamina.

Dickinson R, Lele T Front Cell Dev Biol. 2023; 11:1058727.

PMID: 37397244 PMC: 10308086. DOI: 10.3389/fcell.2023.1058727.

References

Neelam S, Hayes P, Zhang Q, Dickinson R, Lele T . Vertical uniformity of cells and nuclei in epithelial monolayers. Sci Rep. 2016; 6:19689. PMC: 4726213. DOI: 10.1038/srep19689. View

Davidson P, Sliz J, Isermann P, Denais C, Lammerding J . Design of a microfluidic device to quantify dynamic intra-nuclear deformation during cell migration through confining environments. Integr Biol (Camb). 2015; 7(12):1534-46. PMC: 4666765. DOI: 10.1039/c5ib00200a. View

Petrie R, Koo H, Yamada K . Generation of compartmentalized pressure by a nuclear piston governs cell motility in a 3D matrix. Science. 2014; 345(6200):1062-5. PMC: 5248932. DOI: 10.1126/science.1256965. View

Swift J, Ivanovska I, Buxboim A, Harada T, Dingal P, Pinter J . Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science. 2013; 341(6149):1240104. PMC: 3976548. DOI: 10.1126/science.1240104. View

Xiao B, Freedman B, Miller K, Heald R, Marko J . Histone H1 compacts DNA under force and during chromatin assembly. Mol Biol Cell. 2012; 23(24):4864-71. PMC: 3521692. DOI: 10.1091/mbc.E12-07-0518. View

Finan J, Chalut K, Wax A, Guilak F . Nonlinear osmotic properties of the cell nucleus. Ann Biomed Eng. 2008; 37(3):477-91. PMC: 2749482. DOI: 10.1007/s10439-008-9618-5. View

Neelam S, Chancellor T, Li Y, Nickerson J, Roux K, Dickinson R . Direct force probe reveals the mechanics of nuclear homeostasis in the mammalian cell. Proc Natl Acad Sci U S A. 2015; 112(18):5720-5. PMC: 4426403. DOI: 10.1073/pnas.1502111112. View

Thiam H, Vargas P, Carpi N, Crespo C, Raab M, Terriac E . Perinuclear Arp2/3-driven actin polymerization enables nuclear deformation to facilitate cell migration through complex environments. Nat Commun. 2016; 7:10997. PMC: 4796365. DOI: 10.1038/ncomms10997. View

McGregor A, Hsia C, Lammerding J . Squish and squeeze-the nucleus as a physical barrier during migration in confined environments. Curr Opin Cell Biol. 2016; 40:32-40. PMC: 4887392. DOI: 10.1016/j.ceb.2016.01.011. View

10.

Funkhouser C, Sknepnek R, Shimi T, Goldman A, Goldman R, Olvera de la Cruz M . Mechanical model of blebbing in nuclear lamin meshworks. Proc Natl Acad Sci U S A. 2013; 110(9):3248-53. PMC: 3587257. DOI: 10.1073/pnas.1300215110. View

11.

Deguchi S, Maeda K, Ohashi T, Sato M . Flow-induced hardening of endothelial nucleus as an intracellular stress-bearing organelle. J Biomech. 2005; 38(9):1751-9. DOI: 10.1016/j.jbiomech.2005.06.003. View

12.

Allena R, Thiam H, Piel M, Aubry D . A mechanical model to investigate the role of the nucleus during confined cell migration. Comput Methods Biomech Biomed Engin. 2015; 18 Suppl 1:1868-9. DOI: 10.1080/10255842.2015.1070576. View

13.

Stephens A, Banigan E, Adam S, Goldman R, Marko J . Chromatin and lamin A determine two different mechanical response regimes of the cell nucleus. Mol Biol Cell. 2017; 28(14):1984-1996. PMC: 5541848. DOI: 10.1091/mbc.E16-09-0653. View

14.

Giardina C, Renzulli G, Serio G, Caniglia D, Lettini T, Ferri C . Nuclear morphometry in node-negative breast carcinoma. Anal Quant Cytol Histol. 1996; 18(5):374-82. View

15.

Vergani L, Grattarola M, Nicolini C . Modifications of chromatin structure and gene expression following induced alterations of cellular shape. Int J Biochem Cell Biol. 2004; 36(8):1447-61. DOI: 10.1016/j.biocel.2003.11.015. View

16.

Lammerding J, Fong L, Ji J, Reue K, Stewart C, Young S . Lamins A and C but not lamin B1 regulate nuclear mechanics. J Biol Chem. 2006; 281(35):25768-80. DOI: 10.1074/jbc.M513511200. View

17.

Kim D, Li B, Si F, Phillip J, Wirtz D, Sun S . Volume regulation and shape bifurcation in the cell nucleus. J Cell Sci. 2016; 129(2):457. PMC: 6295123. DOI: 10.1242/jcs.185173. View

18.

Elston C, Ellis I . Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991; 19(5):403-10. DOI: 10.1111/j.1365-2559.1991.tb00229.x. View

19.

Versaevel M, Braquenier J, Riaz M, Grevesse T, Lantoine J, Gabriele S . Super-resolution microscopy reveals LINC complex recruitment at nuclear indentation sites. Sci Rep. 2014; 4:7362. PMC: 4258653. DOI: 10.1038/srep07362. View

20.

Jean R, Gray D, Spector A, Chen C . Characterization of the nuclear deformation caused by changes in endothelial cell shape. J Biomech Eng. 2005; 126(5):552-8. DOI: 10.1115/1.1800559. View